Biology subjects

de Navascues, J.

Publications and source records attributed to de Navascues, J..

3 recordsLinked to original sources

bioRxiv2026

Drosben, an affordable system for scalable survival analysis in Drosophila

Survival analysis is a workhorse assay in Drosophila research to evaluate somatic fitness. It is indispensable in the study of ageing and insightful in immunity, metabolism, radiobiology, toxicology, ecology, and others. While conceptually simple, lifespan measurement is labour-intensive because it requires the continuous manual maintenance of large experimental cohorts. Here, we describe Drosben, an approach that combines a 3D-printed device to transfer flies from several vials simultaneously, a paper system for quick data recording and accompanying software that automatically digitalises life tables for analysis. We show that using Drosben reduces the time investment to perform lifespan assays by [~]85%, with improved speed regardless of experience handling Drosophila vials. Using Drosben, we address the effects on longevity of chronic feeding of indole-acetic acid (IAA), naphthalene-acetic acid (NAA) and trimethoprim (TMP) - compounds used to control heterologous targeted protein degradation systems. We find that IAA and NAA have noticeable deleterious effects while TMP has a small protective effect specifically in females. We further show that strong static magnetic fields do not affect Drosophila lifespan. Our work suggests that Drosben can cheaply accelerate research where lifespan is used as a life history trait.

physiology↗

bioRxiv2024

The transcription factor Chronophage/BCL11A/B promotes intestinal stem cell proliferation and endocrine differentiation in the Drosophila intestine

Tissue-resident Adult Stem Cells (ASCs) need to continuously adapt their rate of division and differentiation based on their tissue environment. However, the gene regulatory networks that govern these decisions in ASCs and how they respond to challenges such as infection are often not fully understood. We identify a novel role for the transcription factor (TF) Chronophage (Cph) in ISC proliferation and entero-endocrine (EE) cell differentiation. Cph is a Z2H2 zinc TF orthologous to mammalian BCL11A/B that are involved in regulating adult stem cell fate in various contexts. We show here that Cph is expressed in ISCs and EEs in the Drosophila intestine. Increased levels of Cph correlates with increased ISC proliferation and EE differentiation. cph loss-of-function leads to impaired ISC proliferation. Cph levels are elevated during tumourigenesis as well as in ageing and infection conditions. Knockdown of Cph in a Notch-mutant tumour model reduces tumour size and incidence and extends lifespan. Mechanistically, Cph overexpression leads to an increase in enteroendocrine (EE) cells and DamID DNA-binding and qRT-PCR analysis reveals that Cph directly regulates the levels of key EE regulatory genes such as Prospero (pros) and Phyllopod (phyl). In addition, Cph directly regulates core cell cycle regulators such as E2F1 as well as the TF Nerfin-1 that controls ISC proliferation and maintenance. Together, these data support a role for Cph in finetuning the balance between differentiation and proliferation during entero-endocrine differentiation.

developmental biology↗

bioRxiv2019

Homo- and heterodimerization of bHLH transcription factors balance stemness and bipotential differentiation

Multipotent adult stem cells balance self-renewal with differentiation into various cell types. How this balance is regulated at the transcriptional level is poorly understood. Here we show that a network of basic Helix-Loop-Helix (bHLH) transcription factors controls both stemness and bi-potential differentiation in the Drosophila adult intestine. We find that homodimers of Daughterless (Da), homolog of mammalian E proteins, maintain self-renewal of intestinal stem cells (ISCs), antagonising the Enteroendocrine fate promoted by heterodimers of Da and Scute (Sc, homolog of ASCL). The HLH factor Extramacrochaetae (Emc, homologous to Id proteins) promotes absorptive differentiation by titrating Da and Sc. Emc prevents the committed absorptive progenitor from de-differentiating, underscoring the plasticity of these cells. Switching physical interaction partners in this way enables the active maintenance of stemness while priming stem cells for differentiation along two alternative fates. Such regulatory logic is likely operative in other bipotent stem cell systems.

developmental biology↗